Acta neuropath. (Berl.) 32, 175--186 (1975) 9 by Springer-Verlag 1975 Originalarbeiten
" Original
Investigations
9 Travaux
originaux
Fine Structure of a Cerebellar "Fibroma" Asao t I i r a n o , Josefina F. Llena, a n d H y u n g D. Chung Department of Pathology, Montefiore Hospital and Medical Center, Bronx, New York 10467, and Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461 Received January 13, 1975; Accepted February 13, 1975
Summary. The fine structure of an intracerebellar "fibroma" has been examined. The tumor consists of irregularly-shaped cells connected by well developed junctional complexes. Unusual, fenestrated capillaries with extremely narrow and irregular lumens are frequent. Collagen fibers are not common but the wide extracellular spaces contain large amounts of dense, granular or fibrillar material. The dense material coa~s the tumor cells and is apparently secreted from small vesicles found within these cells. Key words: Fibroma -- Fibroblast -- Junctional Complex -- Blood Vessel.
Introduction The p a u c i t y of connective tissue elements within the central n e r v o u s system is the reason most often given to explain the r a r i t y of "fibromas" i n the brain. Only 12 cases have b e e n r e p o r t e d (Alpers et al., 1932; B a k e r a n d Adams, 1937; Meyer a n d Scheller, 1937; Ziileh, 1956; Amezfia, 1958; B r u e h e r et al., 1970; Koos et al., 1971 ; Kepes et al., 1973; L l e n a et a l , 1975) and, of these, only the most recent has i n v o l v e d the cerebellum (Llena et al., 1975). All the others were w i t h i n the cerebrum. So far as we are aware, the fine structure of these tumors has not been described except for a brief report by Brucher et al. (I 970), who reported the presence
of paramyxovirus-like structures within a tumor in a 42 year old woman. For the most part, however, the morphology of the tumors themselves has been described only at the light microscopic levels. We have examined the fine structure of the intraeerebellar "fibroma" referred to above. The results of that examination form the contents of the present report. Materials and Methods The golfball-sized tumor was totally removed from the left cerebellar hemisphere of a 19 year old man. It was not attached to the dura mater and was encapsulated. Details of the case history and surgical procedure were previously reported (Llena et al., 1975). A portion of the tumor was reserved for electron microscopy. The tissue was fixed in 5% glutaraldehyde in 1/15 M phosphate buffer, ptI 7.4 and postfixed in chrome-osmium. It was embedded in Epon after ethanol dehydration and 2 changes of propylene oxide. Thin sections were prepared, stained in uranyl and lead salts and examined in the electron microscope.
Results The light microscopic findings were reported previously (Llena et al., 1975). Briefly, the tumor consisted of spindle and stellate-shaped cells and had moderate vascularity. There were ample intercellular spaces which were PAS and Aleian blue-positive. Focal aggregates of sudanophilie lipid granules were found in both the tumor and in endothelial cells. 13 Actaneuropath. (Berl.) t~d. 82
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Fig. 1. Irregular tumor cells and their processes are seen in the wide extraeellular spaces, A narrow capillary with an elongated endothelial nucleus (N) traverses the micrograph from the lower left to the upper right ( • 6000)
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Fig.2. T u m o r cells, sometimes attached to one another (arrows) are seen. The extracellular spaces contain a large a m o u n t of moderately dense material ( • 5000)
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Fig. 3. Two tumor cells with g well developed junctional complex. A hemidesmosome (arrow) may also be seen. The cell surfaces are covered with a fibrill~r coating material (•
The electron microscopic observations essentially confirm those made with the light microscope. T h e t u m o r consists of widely separated spindle-shaped cells in spaces containing poorly defined granular and fibrillar material (Figs. 1 and 2). Narrow capillary-like blood vessels were frequently observed (Fig. 1). The spindle-shaped t u m o r cells (Figs. 3 and 4) had elongated nuclei with peripheral ehromatin. Nucleoli were present but not overtly conspicuous. All the expected organelles were present including rough endoplasmic reticulum, Golgi apparatus, mitochondria, free ribosomes, coated vesicles and other small vesicles. The latter were sometimes aggregated and they often contained dense material
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Fig.4. Four desmosome-like structures (large arrows) are seen connecting two tumor cells. A hemidesmosome (small arrow) is also present. Coating material is present at the cell surface ( • 25 000)
(Fig. 5). I n general, t h e y g a v e t h e i m p r e s s i o n of being s e c r e t o r y in n a t u r e . I n addition, areas were p r e s e n t w i t h i n t h e cells which c o n t a i n e d large n u m b e r s of fine fibrils.
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6
Fig,5, Dense granules are present within a tumor cell with coating material at the surface ( • 23000) Fig.6. Fenestrae (arrows) and ~ multilayered basement membrane are seen in this section through a capillary within the tumor (~ 35000)
The cell surfaces h a d c e r t a i n i n t e r e s t i n g features. F r e q u e n t l y , d e s p i t e t h e wide e x t r a c e l l u l a r spaces, the i r r e g u l a r l y - s h a p e d cells were in close c o n t a c t w i t h one a n o t h e r (Figs. 2 - - 4 ) , A t t h e s e regions, one often o b s e r v e d r a t h e r e l a b o r a t e intercellular j u n c t i o n s involving desmosome-like s t r u c t u r e s o f v a r i a b l e lengths w i t h
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Fig. 7. Collagen fibers (large arrow) and finer fibrils (small arrow) are seen in the perivascular space. A basement membrane (BM) is adjacent to the endothelial cell (• 30000)
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Fig. 8. A n a r r o w l u m e n (L) in a capillary. T u b u l a r bodies (arrow) a n d fibrils are seen w i t h i n t h e endothelial cell ( • 25000)
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Fig. 9. Dense granular fibrous mat~ri~l is present in the extracellular space (X 33000)
associated fibrils as well as areas of parallel membrane apposition without pronouneed fibrillar components (Figs. 3 and 4). Frequently, marginal fibrillar condensations similar to hemidesmosomes decorated the inner aspect of the free cell surfaces (Figs. 3 and 4). I n addition, the outer aspects of the Bell surfaces facing the wide extracellular spaces often shouted a finely fibrillar or granular coating material Microvilli-like projections were also seen. Most of the blood vessels seen within the tumor were unusual in t h a t their lumens were very narrow and irregular (Figs.6--8). The endothelial cells were highly elongated and, except for the perinuelear areas, were flattened. Sometimes, the cytoplasm was extremely attenuated and fenestrae were occasionally observed (Fig.6). The-endothelial cytoplasm contained abundant fibrils and scattered elements of the rough endoplasmie reticulum as well as frequent pinoeytotie vesicles. The perinuclear regions contained Golgi apparatus, mitoehondria, tubular bodies (Fig. 8) and mierotubules among other structures. The interendothelial cell junctions were well developed. The basal surfaces of the cells showed occasion-
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al dense, focal condensation of intracellular fibrils and the basal lamina were occasionally multilayered. ]:Iemidesmosome-like structures were also frequent at the basal surface of the cell. As mentioned above, the extracellular spaces were very wide. The background was quite pale but contained an abundance of dense material. Most of this was illdefined fine granular and fibrillar material diffusely spread throughout the spaces. Occasionally, however, conspicuous, dense, aggregates of the granular and fibrillar material were seen (Fig.9). The aggregates showed no periodic structure. Occasional fibrils were present, especially around blood vessels, but these did not constitute a major element of the extracellular material. Occasional fragments of elastic fibers were also observed.
Discussion The present case is an example of an intracranial tumor belonging to the class of non-gliogenous neoplasms described as "fibromas" (Amezfia, 1958; Brucher et al., 1970; Koos et al., 1971), fibroblastomas (Alpers et aI., 1932; Baker and Adams, 1937); fibrous xanthomas (Kepes et al., 1973), or fibromyxomas (Meyer and Scheller, 1937), among others. The origin of these tumors is unknown but it is assumed t h a t they are mesenchymal in nature. I t should be pointed out, however, that the fine structural features of the present tumor are distinctly different from those described in fibromas seen in most other organs (Grossman and Kopilnick, 1971 ; Allegro and Broderick, 1973). I n most of the fibromas previously described at the fine structural level, the extracellular spaces contained abundant collagen fibers. I n the present case, collagen fibers constituted only a minor component of the matrix. Instead, a finely granular and fibrillar material was found in the spaces in the present tumor, which also coated the cell surfaces. This coating material was not, so far as we are aware, described in other fibromas or fibroblastomas. Furthermore, the well development cell junctions which we observed were not reported in most other fibromas although some structures reminiscent of both intercellular junctions and hemidesmosomes have been shown in presumably normal fibroblasts (Fig. 195 in H a u s t and More, 1967). On the other hand, despite what m a y be found in most textbooks, it is often difficult to distinguish between fibroblasts and primitive mesenchymal cells (Movat, 1962). I t is to be noted t h a t young mesenchymal cells can display intercellular adhesive junctions, hemidesmosomes and intracellular fibrils (Parry, 1970). Nevertheless, it might be argued t h a t the cellular origin of the present tumor m a y not have been either fibroblastic or mesenchymal. This tumor was removed from deep within the cerebcllar hemisphere. Thus, it is conceivable t h a t the cell of origin might have been derived from the meninges, a blood vessel or glial cells. Unfortunately, if we consider the fine structure of these other possible candidates for neoplastic transformation, equally good reasons can be offered to cast doubt on them as well. The fine structure of tumors arising from all of these cell types is rather well known and in no case does it resemble the present t u m o r (Poon et al., 1971). For example, none of the tumors of these origins have coating material on the cell surface (Hirano et al., 1971 ; Hirano and Ghatak, 1974). Other differences, too, can be enumerated.
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185
of non-gliogenons neoplasms described as "fibromas" (Amezfia, 1958) origin might have been derived from the meninges, a blood vessel or glial cells. Unfortunately, if we consider the fine structure of these other possible candidates for neoplastie transformation, equally good reasons can be offered to cast doubt on them as well. The fine structure of tumors arising from all of these cell types is rather well known and in no case does it resemble the present tumor (Pooh et al., 1971). For example, none of the tumors of these origins have coating material on the cell surface (Hirano st al., 1971 ; Hirano and Ghatak, 1974). Other differences, too can be enumerated. Another tumor which bears a great resemblance to the present ease at the electron microscopic level are the myxomas described in the left atrium of the heart (Williams et al., 1970; Kelly and Bhagwat, 1972; Ferrans and Roberts, 1973). Although the light microscope revealed certain differences, similar fine structural features, including the surface coating material, were present. These workers also assumed that the coating material was derived from the dense vesicles in the tumor cells (Williams etal., 1970). However, the source of these tumors is also unknown. Their location dictates that only three cell types are likely; namely, fibroblasts, endothelial cells and cardiac muscle_ None of these are totally acceptable candidates since all of them show distinct fine structural differences from the tumor cells just as the cells of the cerebellum differed from the present tumor. A somewhat similar tumor has been described in the subcutaneous tissue of young children (Woyke et al., 1970). Although the origin of the tumor is unknown, the neoplasm was described as an example of fibromatosis (Dreseher et al., 1967). The cells displayed a secretory activity producing fine fibrils which filled the wide extracellular spaces. The cells also contained intraeellular fibrils and, while not described explicitly by the authors, the illustrations clearly show intercellular junctions. Reports of other tumors such as dermatofibroma (Fisher and Vusevski, 1968), malignant fibrous histiocytomas (Fu et al., 1975) and fibroxanthosarcoma (Merkow et al., 1971) have accompanying illustrations that show intercellular relationships closely resembling those found in our ease. Thus, in this case, the electron microscope has raised more questions than it has answered. Only further work with this relatively rare tumor will provide the data needed for some answers.
R e f e r e n ees
Allegra, S. R., Broderiek, P. A.: Desmoid fibroblastoma. Human Path. 4, 419--429 (1973) Alpers, B. J., Yaskin, J. C., Grant, F. C. : Primary fibrob]astoma of the brain. Arch. Neurol. Psychiat. (Chic.) ~7, 270--281 (1932) Amezfia, L. : Fibroma intracerebral gigante recidivado, hibernaci6n artificial. Acta neuropsiquiat, argent. 4, 15--22 (1958) Baker, A. B,, Adams, J. IVI.: Primary fibroblastoma of the brain. Amer. J. Path. 13, 129--137 (1937) Brueher, J. M., Hizawa, K., Wechsler, W. : Ultrastructure d'un fibrome intrac~r~bral et possibilit6 de transformation maligne de ee type tumoral. Rev. neurol. 123, 443--445 (1970) Drescher, E., Woyke, S., Markiewicz, C., Tegi, S. : Juvenile fibromatosis in siblings (Fibromatosis tIyalinica Multiplex Juvenile). J. Pediat. Surg. 2, 427--430 (1967) Ferrans, V. J., Roberts, W.C.: S~ructura[ features of cardiac myxomas: Histology, histochemistry and electron microscopy. Human Path. 4, i 11-146 (i973)
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Fisher, E. 1~., Vusevski, V. D.: Cytogenesis of schwannoma (neurilemoma), neurofibroma, dermatofibroma and dermatofibrosarcoma as revealed by electron microscopy. Amer. J. clin. Path. 49, 141--154 (1968) Fu, Y., Gabbiani, G., Kaye, G. I., Lattes, R. : Malignant soft tissue tumors of probable histiocytie origin (malignant fibrous histiocytomas): General consideration and electron microscopic and tissue culture studies. Cancer 85, 176--198 (1975) Grossman, I. W., Kopilnick, M. D.: Peripelvic renal fibroma : Radiographical, pathological and ultrastructural study of a unique lesion. J. Urol. (Baltimore) 105, 174--176 (1971) Haust, M. D., More, R. H. : Electron microscopy of connective tissues and elastogenesis. In: The Connective Tissue, B. M. Wagner and D. E. Smith (eds.) pp. 352--376. Baltimore: Williams and Wilkins 1967 Hirano, A., Ghatak N. R. : The fine structure of colloid cyst of the third ventricle. J. :Neuropath exp. Neurol. 88, 333--341 (1974) Hirano, A., Ghatak, N. R., Wisoff, Zimmerman, tI. M. : An epithelial cyst of the spinal cord. A n electron microscopic study. Acta neuropath. (Berl.) 18, 214--223 (1971) Kelly, M., Bhagwat, A. G. : Ultrastructural features of a recurrent endothelial myxoma of the left atrium. Arch. Path. 98, 219--226 (1972) Kepes, J. J., Kepes, M., Slowik, F. : Fibrous xanthomas and xanthosarcomas of the meninges and the brain. Acta neuropath. (Berl.) 23, 187--199 (1973) Koos, W. T., Jellinger, K., Sunder-Plassman, M.: Intracercbral fibroma in an ll-month old infant: Case Report. J. Neurosurg. 35, 77--81 (1971) Llena, J. F., Chung, H. D., Hirano, A., Feiring, E. H., Zimmerman, H. M.: Intracerebellar "fibroma." A Case Report. J. Neurosurg. (in press) Merkow, L.P., Frieh, J. C., Jr., Slifkin, M., Kyreages, C. G., Pardo, M. : Ultrastructure of a fibroxanthosarcoma (malignant fibroxanthoma). Cancer 28, 372--383 (1971) Meyer, H. H., Scheller, H.: Uber ein Fibromyxom des Gehirns. Virchow Arch. path. Anat. 800, 473--486 (1937) Movat, I-I. Z. : The fine structure of connective tissue. I. The fibroblast. Exp. molec. Path. 1, 509--534 (1962) Parry, E. W. : Some electron microscope observations on the mesenchymal structures of fullterm umbilical cord. J. Anat. (Lond.) 107, 505--518 (1970) Poon, T. P., Hirano, A., Zimmerman, It. M.: Electron microscopic atlas of brain tumors. :New York-London: Grune and Stratton Inc. 1971 Williams, W. J., Jenkins, D., Erasmus, D. : The ultrastructure of cardiac myxoma. Thorax 25, 756--761 (1970) Woyke, S., Domagala, W., Olszewski, W. : Ultrastructure of a fibromatosis hyalinica multiplex juvenile. Cancer 26, 1157--1168 (1970) Zfilch, K. J. : Fibrome. In: Handbuch der Neurochirurgie. Olivecrona, H., Tonnis, W. (eds) Vo]. 3, p. 467. Berlin-G6ttingen-Heidelberg:Springer 1956 Prof. Dr. A. Hirano Department of Pathology Montefiore Hospital and Medical Center 111 East 210 Street Bronx, :N.Y. 10467, U.S.A.
" Original
Investigations
9 Travaux
originaux
Fine Structure of a Cerebellar "Fibroma" Asao t I i r a n o , Josefina F. Llena, a n d H y u n g D. Chung Department of Pathology, Montefiore Hospital and Medical Center, Bronx, New York 10467, and Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461 Received January 13, 1975; Accepted February 13, 1975
Summary. The fine structure of an intracerebellar "fibroma" has been examined. The tumor consists of irregularly-shaped cells connected by well developed junctional complexes. Unusual, fenestrated capillaries with extremely narrow and irregular lumens are frequent. Collagen fibers are not common but the wide extracellular spaces contain large amounts of dense, granular or fibrillar material. The dense material coa~s the tumor cells and is apparently secreted from small vesicles found within these cells. Key words: Fibroma -- Fibroblast -- Junctional Complex -- Blood Vessel.
Introduction The p a u c i t y of connective tissue elements within the central n e r v o u s system is the reason most often given to explain the r a r i t y of "fibromas" i n the brain. Only 12 cases have b e e n r e p o r t e d (Alpers et al., 1932; B a k e r a n d Adams, 1937; Meyer a n d Scheller, 1937; Ziileh, 1956; Amezfia, 1958; B r u e h e r et al., 1970; Koos et al., 1971 ; Kepes et al., 1973; L l e n a et a l , 1975) and, of these, only the most recent has i n v o l v e d the cerebellum (Llena et al., 1975). All the others were w i t h i n the cerebrum. So far as we are aware, the fine structure of these tumors has not been described except for a brief report by Brucher et al. (I 970), who reported the presence
of paramyxovirus-like structures within a tumor in a 42 year old woman. For the most part, however, the morphology of the tumors themselves has been described only at the light microscopic levels. We have examined the fine structure of the intraeerebellar "fibroma" referred to above. The results of that examination form the contents of the present report. Materials and Methods The golfball-sized tumor was totally removed from the left cerebellar hemisphere of a 19 year old man. It was not attached to the dura mater and was encapsulated. Details of the case history and surgical procedure were previously reported (Llena et al., 1975). A portion of the tumor was reserved for electron microscopy. The tissue was fixed in 5% glutaraldehyde in 1/15 M phosphate buffer, ptI 7.4 and postfixed in chrome-osmium. It was embedded in Epon after ethanol dehydration and 2 changes of propylene oxide. Thin sections were prepared, stained in uranyl and lead salts and examined in the electron microscope.
Results The light microscopic findings were reported previously (Llena et al., 1975). Briefly, the tumor consisted of spindle and stellate-shaped cells and had moderate vascularity. There were ample intercellular spaces which were PAS and Aleian blue-positive. Focal aggregates of sudanophilie lipid granules were found in both the tumor and in endothelial cells. 13 Actaneuropath. (Berl.) t~d. 82
176
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Fig. 1. Irregular tumor cells and their processes are seen in the wide extraeellular spaces, A narrow capillary with an elongated endothelial nucleus (N) traverses the micrograph from the lower left to the upper right ( • 6000)
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Fig.2. T u m o r cells, sometimes attached to one another (arrows) are seen. The extracellular spaces contain a large a m o u n t of moderately dense material ( • 5000)
13"
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Fig. 3. Two tumor cells with g well developed junctional complex. A hemidesmosome (arrow) may also be seen. The cell surfaces are covered with a fibrill~r coating material (•
The electron microscopic observations essentially confirm those made with the light microscope. T h e t u m o r consists of widely separated spindle-shaped cells in spaces containing poorly defined granular and fibrillar material (Figs. 1 and 2). Narrow capillary-like blood vessels were frequently observed (Fig. 1). The spindle-shaped t u m o r cells (Figs. 3 and 4) had elongated nuclei with peripheral ehromatin. Nucleoli were present but not overtly conspicuous. All the expected organelles were present including rough endoplasmic reticulum, Golgi apparatus, mitochondria, free ribosomes, coated vesicles and other small vesicles. The latter were sometimes aggregated and they often contained dense material
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179
Fig.4. Four desmosome-like structures (large arrows) are seen connecting two tumor cells. A hemidesmosome (small arrow) is also present. Coating material is present at the cell surface ( • 25 000)
(Fig. 5). I n general, t h e y g a v e t h e i m p r e s s i o n of being s e c r e t o r y in n a t u r e . I n addition, areas were p r e s e n t w i t h i n t h e cells which c o n t a i n e d large n u m b e r s of fine fibrils.
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6
Fig,5, Dense granules are present within a tumor cell with coating material at the surface ( • 23000) Fig.6. Fenestrae (arrows) and ~ multilayered basement membrane are seen in this section through a capillary within the tumor (~ 35000)
The cell surfaces h a d c e r t a i n i n t e r e s t i n g features. F r e q u e n t l y , d e s p i t e t h e wide e x t r a c e l l u l a r spaces, the i r r e g u l a r l y - s h a p e d cells were in close c o n t a c t w i t h one a n o t h e r (Figs. 2 - - 4 ) , A t t h e s e regions, one often o b s e r v e d r a t h e r e l a b o r a t e intercellular j u n c t i o n s involving desmosome-like s t r u c t u r e s o f v a r i a b l e lengths w i t h
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Fig. 7. Collagen fibers (large arrow) and finer fibrils (small arrow) are seen in the perivascular space. A basement membrane (BM) is adjacent to the endothelial cell (• 30000)
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Fig. 8. A n a r r o w l u m e n (L) in a capillary. T u b u l a r bodies (arrow) a n d fibrils are seen w i t h i n t h e endothelial cell ( • 25000)
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Fig. 9. Dense granular fibrous mat~ri~l is present in the extracellular space (X 33000)
associated fibrils as well as areas of parallel membrane apposition without pronouneed fibrillar components (Figs. 3 and 4). Frequently, marginal fibrillar condensations similar to hemidesmosomes decorated the inner aspect of the free cell surfaces (Figs. 3 and 4). I n addition, the outer aspects of the Bell surfaces facing the wide extracellular spaces often shouted a finely fibrillar or granular coating material Microvilli-like projections were also seen. Most of the blood vessels seen within the tumor were unusual in t h a t their lumens were very narrow and irregular (Figs.6--8). The endothelial cells were highly elongated and, except for the perinuelear areas, were flattened. Sometimes, the cytoplasm was extremely attenuated and fenestrae were occasionally observed (Fig.6). The-endothelial cytoplasm contained abundant fibrils and scattered elements of the rough endoplasmie reticulum as well as frequent pinoeytotie vesicles. The perinuclear regions contained Golgi apparatus, mitoehondria, tubular bodies (Fig. 8) and mierotubules among other structures. The interendothelial cell junctions were well developed. The basal surfaces of the cells showed occasion-
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al dense, focal condensation of intracellular fibrils and the basal lamina were occasionally multilayered. ]:Iemidesmosome-like structures were also frequent at the basal surface of the cell. As mentioned above, the extracellular spaces were very wide. The background was quite pale but contained an abundance of dense material. Most of this was illdefined fine granular and fibrillar material diffusely spread throughout the spaces. Occasionally, however, conspicuous, dense, aggregates of the granular and fibrillar material were seen (Fig.9). The aggregates showed no periodic structure. Occasional fibrils were present, especially around blood vessels, but these did not constitute a major element of the extracellular material. Occasional fragments of elastic fibers were also observed.
Discussion The present case is an example of an intracranial tumor belonging to the class of non-gliogenous neoplasms described as "fibromas" (Amezfia, 1958; Brucher et al., 1970; Koos et al., 1971), fibroblastomas (Alpers et aI., 1932; Baker and Adams, 1937); fibrous xanthomas (Kepes et al., 1973), or fibromyxomas (Meyer and Scheller, 1937), among others. The origin of these tumors is unknown but it is assumed t h a t they are mesenchymal in nature. I t should be pointed out, however, that the fine structural features of the present tumor are distinctly different from those described in fibromas seen in most other organs (Grossman and Kopilnick, 1971 ; Allegro and Broderick, 1973). I n most of the fibromas previously described at the fine structural level, the extracellular spaces contained abundant collagen fibers. I n the present case, collagen fibers constituted only a minor component of the matrix. Instead, a finely granular and fibrillar material was found in the spaces in the present tumor, which also coated the cell surfaces. This coating material was not, so far as we are aware, described in other fibromas or fibroblastomas. Furthermore, the well development cell junctions which we observed were not reported in most other fibromas although some structures reminiscent of both intercellular junctions and hemidesmosomes have been shown in presumably normal fibroblasts (Fig. 195 in H a u s t and More, 1967). On the other hand, despite what m a y be found in most textbooks, it is often difficult to distinguish between fibroblasts and primitive mesenchymal cells (Movat, 1962). I t is to be noted t h a t young mesenchymal cells can display intercellular adhesive junctions, hemidesmosomes and intracellular fibrils (Parry, 1970). Nevertheless, it might be argued t h a t the cellular origin of the present tumor m a y not have been either fibroblastic or mesenchymal. This tumor was removed from deep within the cerebcllar hemisphere. Thus, it is conceivable t h a t the cell of origin might have been derived from the meninges, a blood vessel or glial cells. Unfortunately, if we consider the fine structure of these other possible candidates for neoplastic transformation, equally good reasons can be offered to cast doubt on them as well. The fine structure of tumors arising from all of these cell types is rather well known and in no case does it resemble the present t u m o r (Poon et al., 1971). For example, none of the tumors of these origins have coating material on the cell surface (Hirano et al., 1971 ; Hirano and Ghatak, 1974). Other differences, too, can be enumerated.
Fine Structure of a Cerebellar "Fibroma"
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of non-gliogenons neoplasms described as "fibromas" (Amezfia, 1958) origin might have been derived from the meninges, a blood vessel or glial cells. Unfortunately, if we consider the fine structure of these other possible candidates for neoplastie transformation, equally good reasons can be offered to cast doubt on them as well. The fine structure of tumors arising from all of these cell types is rather well known and in no case does it resemble the present tumor (Pooh et al., 1971). For example, none of the tumors of these origins have coating material on the cell surface (Hirano st al., 1971 ; Hirano and Ghatak, 1974). Other differences, too can be enumerated. Another tumor which bears a great resemblance to the present ease at the electron microscopic level are the myxomas described in the left atrium of the heart (Williams et al., 1970; Kelly and Bhagwat, 1972; Ferrans and Roberts, 1973). Although the light microscope revealed certain differences, similar fine structural features, including the surface coating material, were present. These workers also assumed that the coating material was derived from the dense vesicles in the tumor cells (Williams etal., 1970). However, the source of these tumors is also unknown. Their location dictates that only three cell types are likely; namely, fibroblasts, endothelial cells and cardiac muscle_ None of these are totally acceptable candidates since all of them show distinct fine structural differences from the tumor cells just as the cells of the cerebellum differed from the present tumor. A somewhat similar tumor has been described in the subcutaneous tissue of young children (Woyke et al., 1970). Although the origin of the tumor is unknown, the neoplasm was described as an example of fibromatosis (Dreseher et al., 1967). The cells displayed a secretory activity producing fine fibrils which filled the wide extracellular spaces. The cells also contained intraeellular fibrils and, while not described explicitly by the authors, the illustrations clearly show intercellular junctions. Reports of other tumors such as dermatofibroma (Fisher and Vusevski, 1968), malignant fibrous histiocytomas (Fu et al., 1975) and fibroxanthosarcoma (Merkow et al., 1971) have accompanying illustrations that show intercellular relationships closely resembling those found in our ease. Thus, in this case, the electron microscope has raised more questions than it has answered. Only further work with this relatively rare tumor will provide the data needed for some answers.
R e f e r e n ees
Allegra, S. R., Broderiek, P. A.: Desmoid fibroblastoma. Human Path. 4, 419--429 (1973) Alpers, B. J., Yaskin, J. C., Grant, F. C. : Primary fibrob]astoma of the brain. Arch. Neurol. Psychiat. (Chic.) ~7, 270--281 (1932) Amezfia, L. : Fibroma intracerebral gigante recidivado, hibernaci6n artificial. Acta neuropsiquiat, argent. 4, 15--22 (1958) Baker, A. B,, Adams, J. IVI.: Primary fibroblastoma of the brain. Amer. J. Path. 13, 129--137 (1937) Brueher, J. M., Hizawa, K., Wechsler, W. : Ultrastructure d'un fibrome intrac~r~bral et possibilit6 de transformation maligne de ee type tumoral. Rev. neurol. 123, 443--445 (1970) Drescher, E., Woyke, S., Markiewicz, C., Tegi, S. : Juvenile fibromatosis in siblings (Fibromatosis tIyalinica Multiplex Juvenile). J. Pediat. Surg. 2, 427--430 (1967) Ferrans, V. J., Roberts, W.C.: S~ructura[ features of cardiac myxomas: Histology, histochemistry and electron microscopy. Human Path. 4, i 11-146 (i973)
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Fisher, E. 1~., Vusevski, V. D.: Cytogenesis of schwannoma (neurilemoma), neurofibroma, dermatofibroma and dermatofibrosarcoma as revealed by electron microscopy. Amer. J. clin. Path. 49, 141--154 (1968) Fu, Y., Gabbiani, G., Kaye, G. I., Lattes, R. : Malignant soft tissue tumors of probable histiocytie origin (malignant fibrous histiocytomas): General consideration and electron microscopic and tissue culture studies. Cancer 85, 176--198 (1975) Grossman, I. W., Kopilnick, M. D.: Peripelvic renal fibroma : Radiographical, pathological and ultrastructural study of a unique lesion. J. Urol. (Baltimore) 105, 174--176 (1971) Haust, M. D., More, R. H. : Electron microscopy of connective tissues and elastogenesis. In: The Connective Tissue, B. M. Wagner and D. E. Smith (eds.) pp. 352--376. Baltimore: Williams and Wilkins 1967 Hirano, A., Ghatak N. R. : The fine structure of colloid cyst of the third ventricle. J. :Neuropath exp. Neurol. 88, 333--341 (1974) Hirano, A., Ghatak, N. R., Wisoff, Zimmerman, tI. M. : An epithelial cyst of the spinal cord. A n electron microscopic study. Acta neuropath. (Berl.) 18, 214--223 (1971) Kelly, M., Bhagwat, A. G. : Ultrastructural features of a recurrent endothelial myxoma of the left atrium. Arch. Path. 98, 219--226 (1972) Kepes, J. J., Kepes, M., Slowik, F. : Fibrous xanthomas and xanthosarcomas of the meninges and the brain. Acta neuropath. (Berl.) 23, 187--199 (1973) Koos, W. T., Jellinger, K., Sunder-Plassman, M.: Intracercbral fibroma in an ll-month old infant: Case Report. J. Neurosurg. 35, 77--81 (1971) Llena, J. F., Chung, H. D., Hirano, A., Feiring, E. H., Zimmerman, H. M.: Intracerebellar "fibroma." A Case Report. J. Neurosurg. (in press) Merkow, L.P., Frieh, J. C., Jr., Slifkin, M., Kyreages, C. G., Pardo, M. : Ultrastructure of a fibroxanthosarcoma (malignant fibroxanthoma). Cancer 28, 372--383 (1971) Meyer, H. H., Scheller, H.: Uber ein Fibromyxom des Gehirns. Virchow Arch. path. Anat. 800, 473--486 (1937) Movat, I-I. Z. : The fine structure of connective tissue. I. The fibroblast. Exp. molec. Path. 1, 509--534 (1962) Parry, E. W. : Some electron microscope observations on the mesenchymal structures of fullterm umbilical cord. J. Anat. (Lond.) 107, 505--518 (1970) Poon, T. P., Hirano, A., Zimmerman, It. M.: Electron microscopic atlas of brain tumors. :New York-London: Grune and Stratton Inc. 1971 Williams, W. J., Jenkins, D., Erasmus, D. : The ultrastructure of cardiac myxoma. Thorax 25, 756--761 (1970) Woyke, S., Domagala, W., Olszewski, W. : Ultrastructure of a fibromatosis hyalinica multiplex juvenile. Cancer 26, 1157--1168 (1970) Zfilch, K. J. : Fibrome. In: Handbuch der Neurochirurgie. Olivecrona, H., Tonnis, W. (eds) Vo]. 3, p. 467. Berlin-G6ttingen-Heidelberg:Springer 1956 Prof. Dr. A. Hirano Department of Pathology Montefiore Hospital and Medical Center 111 East 210 Street Bronx, :N.Y. 10467, U.S.A.
